The overall objective of this Program Project Grant is to study the regulation of the circulation in pathological states. The main theme is neuro-humoral control of the circulation. The Program represents the coordinated effort of clinical and basic investigators to study the cellular and cardiovascular control mechanisms underlying abnormalities of circulatory regulation in pathologic states such as hypertension, cardiac hypertrophy and failure and myocardial ischemia. The research on cellular mechanisms includes studies on the electrophysiologic properties and reactivity of arterial muscle in hypertension; biochemical determinants of contraction in vascular and cardiac muscle, and the regulation of sodium and chloride transport. Research in cardiovascular control mechanisms emphasized autonomic, humoral, and renal factors in pathologic states and the regulation of myocardial performance during ischemia and mechanical stresses. This program was originally awarded in 1971 and renewed in 1976 for an additional five years. The goals of the supplement are: 1) to provide support for the continuation of two research directions approved at the time of the competitive renewal in 1976 for only two or three years; one deals with basic renal mechanisms and the other with the development and testing of an analytical model of left ventricular contraction; 2) to integrate into the Program Project Grant expertise on new investigators, some of whom are new recruits, to our Cardiovascular Center, who will add depth to the research programs in the areas of cardiac biochemistry; CNS control of hypertension; the structural and functional consequences of myocardial unloading and the baroreceptor reflex in heart failure.